Histochemical detection of intranuclear DNA fragmentation and its relation to the expression of bcl‐2 oncoprotein in human prostatic cancer

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Abstract
To assess the incidence of intranuclear DNA fragmentation and the expression of the bcl-2 oncoprotein in prostatic carcinoma, both of which are related to programmed cell death. Specimens of tumour obtained from 17 patients with newly diagnosed prostatic carcinoma and 16 with hormone-treated prostatic carcinoma undergoing total prostatectomy were evaluated. DNA fragmentation was detected using the terminal-labelling method (d-uridine triphosphate conjugated with digoxigenin) and the expression of bcl-2 was detected immunohistochemically. There was a high incidence of intranuclear DNA fragmentation in 14 of 17 untreated tumours and 15 of 16 hormone-treated tumours. There were no differences between the positive cases in hormone-treated tumours and untreated tumours. There was significantly greater expression of bcl-2 in tumours treated with non-steroidal anti-androgen drugs (eight of nine were positive) than in those untreated (seven of 17) or treated with other drugs (one of seven) (P < 0.05). There was a consistent and marked dissociation between DNA fragmentation and bcl-2 positivity; most of the cells positive for bcl-2 showed no DNA fragmentation. The results indicated that cells positive for bcl-2 might potentially be hormone resistant and that the administration of non-steroidal anti-androgen drugs might have a role in the induction of hormone-resistant cells.

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